Malaria infects 200-400 million people each year causing 1-2 million deaths, thus remaining one of the most important infectious diseases in the world. Approximately 25 percent of all deaths of children in rural Africa between the ages of one and four years are caused by malaria. Due to the importance of the disease as a worldwide health problem, considerable effort is being expended to identify and develop malaria vaccines.
Malaria in humans is caused by four species of the parasite Plasmodium: P. falciparum, P. vivax, P. knowlesi and P. malariae. The major cause of malaria in humans is P. falciparum which infects 200 million to 400 million people every year, killing 1 to 4 million.
Duffy Antigen Binding Protein (DABP) and Sialic Acid Binding Protein (SABP) are soluble proteins that appear in the culture supernatant after infected erythrocytes release merozoites. Immunochemical data indicate that DABP and SABP which are the respective ligands for the P. vivax and P. falciparum Duffy and sialic acid receptors on erythrocytes, possess specificities of binding which are identical either in soluble or membrane bound form.
DABP is a 135 kDa protein which binds specifically to Duffy blood group determinants (Wertheimer et al., Exp. Parasitol. 69: 340-350 (1989); Barnwell, et al., J. Exp. Med. 169: 1795-1802 (1989)). Thus, binding of DABP is specific to human Duffy positive erythrocytes. There are four major Duffy phenotypes for human erythrocytes: Fy(a), Fy(b), Fy(ab) and Fy(negative), as defined by the anti-Fy.sup.a and anti-Fy.sup.b sera (Hadley et al., In Red Cell Antigens and Antibodies, G. Garratty, ed. (Arlington, Va.:American Association of Blood Banks) pp. 17-33 (1986)). DABP binds equally to both Fy(a) and Fy(b) erythrocytes which are equally susceptible to invasion by P. vivax; but not to Fy(negative) erythrocytes.
In the case of SABP, a 175 kDa protein, binding is specific to the glycophorin sialic acid residues on erythrocytes (Camus and Hadley, Science 230:553-556 (1985); Orlandi, et al., J. Cell Biol. 116:901-909 (1992)). Thus, neuraminidase treatment (which cleaves off sialic acid residues) render erythrocytes immune to P. falciparum invasion.
The specificities of binding and correlation to invasion by the parasite thus indicate that DABP and SABP are the proteins of P. vivax and P. falciparum which interact with sialic acids and the Duffy antigen on the erythrocyte. The genes encoding both proteins have been cloned and the DNA and predicted protein sequences have been determined (B. Kim Lee Sim, et al., J. Cell Biol. 111: 1877-1884 (1990); Fang, X., et al., Mol. Biochem Parasitol. 44: 125-132 (1991)).
Despite considerable research efforts worldwide, because of the complexity of the Plasmodium parasite and its interaction with its host, it has not been possible to discover a satisfactory solution for prevention or abatement of the blood stage of malaria. Because malaria is a such a large worldwide health problem, there is a need for methods that abate the impact of this disease. The present invention provides effective preventive and therapeutic measures against Plasmodium invasion.